FACULTY AWARDS 10
NSF CAREER AWARD
Gleghorn to develop micro-sized devices to understand the body’s immune system Jason Gleghorn, an associate
professor, received a National Science Foundation (NSF) CAREER Award to understand how the body’s adaptive immune system activates. He is developing a new class of microfluidic devices to culture an entire lymph node outside the body and study the cells’ behavior in real time. The work has broad application to the understanding of chronic infection and inflammation, and metastatic cancer to the lymph node. It also could inform drug delivery strategies for chemotherapy and antiretroviral therapies for HIV. A lymph node’s complex structure prevents drugs from penetrating inside to target viruses, bacteria and
University of Delaware
metastatic cancer cells that collect there. Gleghorn is interested in how immune cells go through the lymph node, and how these immune cells work and behave. “Sometimes cells bring viruses like HIV and bacteria into the lymph node. When these foreign invaders, or metastatic tumor cells themselves, move into privileged areas called lobules within the lymph node, the drugs that work well in the rest of the body cannot get in to kill the infection,” said Gleghorn. “We believe this is why you get recurrence of viral infection like HIV and why cancer metastasis to lymph nodes is so devastating. To-date there is no tractable way to solve this problem; we do not know how this works.” Gleghorn is developing experimental devices that can enable researchers to see, understand and image how things work and behave in the more complex organ in real time. Initial work on the project will include developing the system to culture an
entire lymph node with collaborators at University of Pennsylvania’s School of Veterinary Medicine, a unique approach that will allow the researchers to retain the organ’s complexity in its natural state. Then, in collaboration with Penn Medicine’s transplant team, Gleghorn’s research team will advance the system to enable culture and imaging of human lymph nodes. The UD-developed device will be made from molded silicon rubber and tiny glass needles that the researchers make. They will load the lymph node into the middle of the mold, then connect the teeny-tiny glass tubes into the blood and lymphatic vessels that go into and out of the lymph node. Using this “plumbing” the team plans to insert specific cells or drugs and track them as they move through the lymph node. The team will collect real-time measurements to validate that what they see in this new whole-organ culture system actually replicates what can be expected inside the body.
